HRP20140922T1 - Method for preparing nebivolol - Google Patents

Method for preparing nebivolol Download PDF

Info

Publication number
HRP20140922T1
HRP20140922T1 HRP20140922AT HRP20140922T HRP20140922T1 HR P20140922 T1 HRP20140922 T1 HR P20140922T1 HR P20140922A T HRP20140922A T HR P20140922AT HR P20140922 T HRP20140922 T HR P20140922T HR P20140922 T1 HRP20140922 T1 HR P20140922T1
Authority
HR
Croatia
Prior art keywords
formula
compound
halogenmethyllithium
derivative
image
Prior art date
Application number
HRP20140922AT
Other languages
Croatian (hr)
Inventor
Yvon Derrien
Eric Chenard
Alain Burgos
Original Assignee
Zach System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zach System filed Critical Zach System
Publication of HRP20140922T1 publication Critical patent/HRP20140922T1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/66—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (16)

1. Postupak dobivanja spoja formule [image] , gdje je X atom halogena, naznačen time što se sastoji u reakciji spoja formule [image] , gdje je R (C1-C6)-alkilna skupina, s derivatom halogenmetillitija formule Li-CH2-X, u kojoj je X definiran kao gore.1. Procedure for obtaining the compound of the formula [image] , where X is a halogen atom, characterized by the fact that it consists in the reaction of a compound of the formula [image] , where R is a (C1-C6)-alkyl group, with a halomethyllithium derivative of the formula Li-CH2-X, wherein X is as defined above. 2. Postupak u skladu s patentnim zahtjevom 1, naznačen time što se derivat halogenmetillitija dobiva u reakcijskom sustavu.2. The method according to claim 1, characterized in that the halogenmethyllithium derivative is obtained in a reaction system. 3. Postupak u skladu s patentnim zahtjevom 2, naznačen time što se derivat halogenmetillitija dobiva dodavanjem organolitijskog reagensa dihalogenmetanu.3. The method according to claim 2, characterized in that the halogenmethyllithium derivative is obtained by adding an organolithium reagent to dihalogenomethane. 4. Postupak u skladu s patentnim zahtjevom 3, naznačen time što je dihalogenmetan bromklormetan.4. The method according to claim 3, characterized in that the dihalomethane is bromochloromethane. 5. Postupak u skladu s patentnim zahtjevom 3 ili zahtjevom 4, naznačen time što je organolitijski reagens n-butillitij.5. The method according to claim 3 or claim 4, characterized in that the organolithium reagent is n-butyllithium. 6. Postupak u skladu s bilo kojim od patentnih zahtjeva 3 do 5, naznačen time što se spoj formule (VI), dihalogenmetan i organolitijski reagens upotrebljava u molarnom omjeru od otprilike 1:2:2.6. The method according to any of claims 3 to 5, characterized in that the compound of formula (VI), dihalomethane and organolithium reagent are used in a molar ratio of approximately 1:2:2. 7. Postupak u skladu s bilo kojim od prethodnih zahtjeva, naznačen time što je derivat halogenmetillitija klormetillitij.7. Process according to any of the preceding claims, characterized in that the halogenmethyllithium derivative is chloromethyllithium. 8. Postupak u skladu s bilo kojim od prethodnih zahtjeva, naznačen time što se reakciju spoja formule VI s derivatom halogenmetillitija provodi u prisutnosti otapala.8. Process according to any of the preceding claims, characterized in that the reaction of the compound of formula VI with the halogenmethyllithium derivative is carried out in the presence of a solvent. 9. Postupak u skladu s patentnim zahtjevom 8, naznačen time što je otapalo tetrahidrofuran (THF).9. The method according to claim 8, characterized in that the solvent is tetrahydrofuran (THF). 10. Postupak u skladu s patentnim zahtjevom 1, naznačen time što se dodavanje halogenmetillitija spoju formule (VI) provodi u rasponu temperatura od –100 °C do 0 °C.10. The process according to claim 1, characterized in that the addition of halogenmethyllithium to the compound of formula (VI) is carried out in the temperature range from -100 °C to 0 °C. 11. Postupak u skladu s patentnim zahtjevom 10, naznačen time što se dodavanje halogenmetillitija provodi u rasponu temperatura od –85 °C do –50 °C.11. The process according to claim 10, characterized in that the addition of halogenmethyllithium is carried out in the temperature range from -85 °C to -50 °C. 12. Postupak dobivanja spoja formule [image] , naznačen time što se sastoji u prevođenju spoja formule (VI) u spoj formule (I) postupkom u skladu s patentnim zahtjevom 1.12. Procedure for obtaining the compound of the formula [image] , characterized by the fact that it consists in the conversion of the compound of formula (VI) into the compound of formula (I) by a process in accordance with patent claim 1. 13. Postupak u skladu s patentnim zahtjevom 12, naznačen time što se dodatno sastoji u reduciranju spoja formule I kako bi se dobilo spoj formule (VIII): [image] , u kojoj je X atom halogena, i reakciji navedenog spoja formule (VIII) s bazom kako bi se dobilo epoksidni spoj formule (VII).13. The method according to patent claim 12, characterized in that it additionally consists in reducing the compound of formula I to obtain the compound of formula (VIII): [image] , in which X is a halogen atom, i reaction of the specified compound of formula (VIII) with a base to obtain an epoxy compound of formula (VII). 14. Postupak dobivanja spoja formule [image] , naznačen time što se sastoji u reakciji spoja formule [image] , u kojoj je R (C1-C6)-alkilna skupina, s derivatom halogenmetillitija formule Li-CH2-X, u kojoj je X atom halogena, kako bi se dobilo reakcijsku smjesu; reduciranju navedene reakcijske smjese na licu mjesta; i cikliziranju u prisutnosti baze.14. Procedure for obtaining the compound of the formula [image] , characterized by the fact that it consists in the reaction of a compound of the formula [image] , wherein R is a (C1-C6)-alkyl group, with a halomethyllithium derivative of the formula Li-CH2-X, wherein X is a halogen atom, to give a reaction mixture; reduction of the said reaction mixture on the spot; and cyclization in the presence of a base. 15. Postupak dobivanja nebivolola, naznačen time što se sastoji u prevođenju spoja formule (VI) u spoj formule (I) postupkom u skladu s patentnim zahtjevom 1.15. The process for obtaining nebivolol, characterized in that it consists in the conversion of the compound of formula (VI) into the compound of formula (I) by the process in accordance with patent claim 1. 16. Postupak dobivanja nebivolola, naznačen time što se sastoji u prevođenju u jednoj posudi spoja formule (VI) u spoj formule (VII) postupkom u skladu s patentnim zahtjevom 14.16. The process for obtaining nebivolol, characterized by the fact that it consists in converting the compound of formula (VI) into the compound of formula (VII) in one container by the process according to patent claim 14.
HRP20140922AT 2008-09-24 2014-09-26 Method for preparing nebivolol HRP20140922T1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0856415 2008-09-24
PCT/FR2009/051775 WO2010034927A1 (en) 2008-09-24 2009-09-22 Method for preparing nebivolol

Publications (1)

Publication Number Publication Date
HRP20140922T1 true HRP20140922T1 (en) 2014-11-07

Family

ID=40527387

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20140922AT HRP20140922T1 (en) 2008-09-24 2014-09-26 Method for preparing nebivolol

Country Status (12)

Country Link
US (1) US8981127B2 (en)
EP (1) EP2328883B1 (en)
JP (1) JP5744738B2 (en)
CN (1) CN102164906A (en)
AU (1) AU2009295730B2 (en)
BR (1) BRPI0919257B8 (en)
CA (1) CA2736600C (en)
ES (1) ES2523343T3 (en)
HR (1) HRP20140922T1 (en)
IL (1) IL211410A (en)
PL (1) PL2328883T3 (en)
WO (1) WO2010034927A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102180855B (en) * 2011-03-01 2015-11-25 浙江华海药业股份有限公司 A kind of method of purification of Nebivolol Intermediates
ITRM20110418A1 (en) 2011-08-02 2013-02-03 Menarini Int Operations Lu Sa PROCESS FOR THE PREPARATION OF EPOXY WHICH INTERMEDIATES FOR THE SYNTHESIS OF NEBIVOLOL.
EP2907809B1 (en) 2014-02-14 2018-08-22 Corden Pharma International GmbH Base-free process for the preparation of ketone intermediates usable for manufacture of nebivolol
CN104610215A (en) * 2015-01-19 2015-05-13 浙江海翔药业股份有限公司 Preparation method of nebivolol intermediates and preparation method of nebivolol
ITUB20160227A1 (en) 2016-01-21 2017-07-21 Menarini Int Operations Luxembourg Sa Process for the synthesis of Nebivolol intermediates
CN108997297B (en) * 2018-07-17 2020-12-01 浙江海翔药业股份有限公司 Preparation method of nebivolol intermediate, intermediate for preparing nebivolol intermediate and preparation method of nebivolol intermediate

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5591885A (en) * 1994-09-23 1997-01-07 Hoffman-La Roche Inc. Process for the preparation of halogenated α-aminoketone compounds
US5523463A (en) * 1994-09-23 1996-06-04 Hoffmann-La Roche Inc. Method of producing halogenated and alpha-aminoalchohols
US6127556A (en) * 1996-12-31 2000-10-03 G. D. Searle & Co. Epoxide formation by continuous in-situ synthesis process
WO2004002409A2 (en) * 2002-06-27 2004-01-08 Nitromed, Inc. Cyclooxygenase-2 selective inhibitors, compositions and methods of use
US8030339B2 (en) * 2005-10-14 2011-10-04 Neurosearch A/S Imidazole derivatives for the treatment of anxiety and related diseases
US7560575B2 (en) * 2005-12-28 2009-07-14 Acino Pharma Ag Process for preparation of racemic Nebivolol
ITMI20061889A1 (en) * 2006-10-03 2008-04-04 Zambon Spa NEBIVOLOL PREPARATION PROCESS
EP2061759B1 (en) * 2006-10-04 2013-03-27 Bristol-Myers Squibb Company Cyclic modulators of chemokine receptor activity
MX2010000334A (en) * 2007-06-28 2010-04-22 Intervet Int Bv Substituted piperazines as cb1 antagonists.

Also Published As

Publication number Publication date
IL211410A0 (en) 2011-05-31
WO2010034927A1 (en) 2010-04-01
CA2736600A1 (en) 2010-04-01
CA2736600C (en) 2017-03-21
AU2009295730A1 (en) 2010-04-01
EP2328883B1 (en) 2014-08-06
PL2328883T3 (en) 2015-01-30
US8981127B2 (en) 2015-03-17
CN102164906A (en) 2011-08-24
BRPI0919257B8 (en) 2021-05-25
AU2009295730B2 (en) 2013-12-19
JP2012503636A (en) 2012-02-09
BRPI0919257B1 (en) 2021-05-04
EP2328883A1 (en) 2011-06-08
IL211410A (en) 2015-10-29
BRPI0919257A2 (en) 2015-08-18
JP5744738B2 (en) 2015-07-08
ES2523343T3 (en) 2014-11-25
US20110237808A1 (en) 2011-09-29

Similar Documents

Publication Publication Date Title
HRP20140922T1 (en) Method for preparing nebivolol
CA2510093A1 (en) Novel process for the preparation of.alpha.-chlorovinyl, .alpha.,.alpha.-dichloro, and acetylenes from ketones
MY198064A (en) Method for preparing 3-trifluoromethyl chalcones
PE20060649A1 (en) POLYMORPHIC FORM II OF RAPAMYCIN AND PREPARATION PROCESS
NO20092960L (en) Crystalline minocycline base and processes for its preparation
Imai et al. First catalytic and enantioselective synthesis of silyl and stannyl substituted cyclopropylmethanols
Xie et al. Efficient and mild synthesis of functionalized 2, 3-dihydrofuran derivatives via domino reaction in water
HRP20110418T1 (en) Crystallisation of solid forms of clopidogrel addition salts
EP2178871A2 (en) Cyclic ethers
JP2011519860A5 (en)
HRP20160740T1 (en) Process for preparing nebivolol
Liang et al. Catalytic asymmetric brominative dearomatization reaction of benzofurans
Yang et al. Saprotrophic fungal diversity predicts ectomycorrhizal fungal diversity along the timberline in the framework of island biogeography theory
ATE286853T1 (en) MICROPOROUS CRYSTALLINE MATERIAL (ITQ-15), METHOD FOR THE PRODUCTION THEREOF AND ITS USE IN PROCESSES FOR SEPARATION AND CONVERSION OF ORGANIC COMPOUNDS
JP2009292749A (en) Method for producing fluorinated organic compound
JP2016535033A (en) Cross-coupling of non-activated secondary boronic acids
CN112940036B (en) Preparation method of benzothiazole phosphate compound
WO2010011546A3 (en) Pyrrolo [3, 2-b]pyridines and pyrazolo [4, 3 -b] pyridines having 5-ht6 receptor affinity
Pandey et al. Imino-ene reaction of N-tosyl arylaldimines with α-methylstyrene: application in the synthesis of important amines
Mandai et al. Bacteriogenic iron oxide as an effective catalyst for Baeyer-Villiger oxidation with molecular oxygen and benzaldehyde
CN106928165A (en) A kind of preparation method of tetrahydrofurfuryl ethers compound
WO2007077485A3 (en) Method for producing metallocenes
HRP20141087T1 (en) Synthetic intermediate of oxazole compound and method for producing the same
WO2009079578A8 (en) Low voc waterbased coatings with efflorescence resistance
Canoa et al. The furan approach to oxacycles. Part 6: From THF to fused polyoxepanes